Recombinant human arginase inhibits the in vitro and in vivo proliferation of human melanoma by inducing cell cycle arrest and apoptosis

Tin Lun Lam, Gabriel K.Y. Wong, Ho Yin Chow, Hiu Chi Chong, Tsz Lung Chow, Sui Yi Kwok, Paul N.M. Cheng, Denys N. Wheatley, Wai Hung Lo, Yun Chung Leung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

67 Citations (Scopus)


Melanoma has been shown to require arginine for growth, thus providing a potential Achilles' heel for therapeutic exploitation. Our investigations show that arginine depletion, using a recombinant form of human arginase I (rhArg), efficiently inhibits the growth of mammalian melanoma cell lines in vitro. These cell lines are consistently deficient in ornithine transcarbamylase (OTC) expression, correlating with their sensitivity to rhArg. Cell cycle distribution of A375 human melanoma cells treated with rhArg showed a remarkable dual-phase cell cycle arrest in S and G2/M phases, in contrast to the G2/M single-phase arrest observed with arginine deiminase (ADI), another arginine-degrading enzyme. rhArg and ADI both induced substantial apoptosis in A375 cells, accompanied by global modulation of cell cycle- and apoptosis-related transcription. Moreover, PEGylated rhArg dramatically inhibited the growth of A375 and B16 melanoma xenografts in vivo. Our results establish for the first time that (PEGylated) rhArg is a promising candidate for effective melanoma treatment, with fewer safety issues than ADI. Insight into the mechanism behind the antiproliferative activity of rhArg could inform us in designing combination therapies for future clinical trials.
Original languageEnglish
Pages (from-to)366-376
Number of pages11
JournalPigment Cell and Melanoma Research
Issue number2
Publication statusPublished - 1 Apr 2011


  • Apoptosis
  • Arginase
  • Cell cycle
  • Melanoma
  • PEGylated enzyme

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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